title: Heme oxygenase-1 prevents cardiac dysfunction in streptozotocin-diabetic mice by reducing inflammation, oxidative stress, apoptosis and enhancing autophagy.
abstract: Heme oxygenase-1 (HO-1) has been implicated in cardiac dysfunction, oxidative stress, inflammation, apoptosis and autophagy associated with heart failure, and atherosclerosis, in addition to its recognized role in metabolic syndrome and diabetes. Numerous studies have presented contradictory findings about the role of HO-1 in diabetic cardiomyopathy (DCM). In this study, we explored the role of HO-1 in myocardial dysfunction, myofibril structure, oxidative stress, inflammation, apoptosis and autophagy using a streptozotocin (STZ)-induced diabetes model in mice systemically overexpressing HO-1 (Tg-HO-1) or mutant HO-1 (Tg-mutHO-1). The diabetic mouse model was induced by multiple peritoneal injections of STZ. Two months after injection, left ventricular (LV) function was measured by echocardiography. In addition, molecular biomarkers related to oxidative stress, inflammation, apoptosis and autophagy were evaluated using classical molecular biological/biochemical techniques. Mice with DCM exhibited severe LV dysfunction, myofibril structure disarray, aberrant cardiac oxidative stress, inflammation, apoptosis, autophagy and increased levels of HO-1. In addition, we determined that systemic overexpression of HO-1 ameliorated left ventricular dysfunction, myofibril structure disarray, oxidative stress, inflammation, apoptosis and autophagy in DCM mice. Furthermore, serine/threonine-specific protein kinase (Akt) and AMP-activated protein kinase (AMPK) phosphorylation is normally inhibited in DCM, but overexpression of the HO-1 gene restored the phosphorylation of these kinases to normal levels. In contrast, the functions of HO-1 in DCM were significantly reversed by overexpression of mutant HO-1. This study underlines the unique roles of HO-1, including the inhibition of oxidative stress, inflammation and apoptosis and the enhancement of autophagy, in the pathogenesis of DCM.
authors.affiliation: Department of Biochemistry, Harbin Medical University, Harbin, Heilongjiang, China ; Department of Biochemistry, Medical College of Qinghai University, Xining, Qinghai, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhao
authors.forename: Lina
authors.initials: L
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Qiao
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhou
authors.forename: Guodong
authors.initials: G
authors.lastname: Wu
authors.forename: Lujing
authors.initials: L
authors.lastname: Wang
authors.forename: Yahui
authors.initials: Y
authors.lastname: Peng
authors.forename: Xingli
authors.initials: X
authors.lastname: Dong
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.forename: Lining
authors.initials: L
authors.lastname: Si
authors.forename: Xueying
authors.initials: X
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Jihong
authors.initials: J
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Lingyun
authors.initials: L
authors.lastname: Zhou
authors.forename: Xu
authors.initials: X
authors.lastname: Gao
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology; D015153:Blotting, Western; D017931:DNA Primers / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D004452:Echocardiography; D005786:Gene Expression Regulation / Q000235:genetics*; D006331:Heart Diseases / Q000201:enzymology / Q000517:prevention & control*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013311:Streptozocin / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D017931:DNA Primers; D017382:Reactive Oxygen Species; D013311:Streptozocin; D051547:Heme Oxygenase-1